Outcomes of Treatment for Achalasia Depend on Manometric Subtype

Wout O. Rohof; Renato Salvador; Vito Annese; Stanislas Bruley Des Varannes; Stanislas Chaussade; Mario Costantini; J. Ignasi Elizalde; Marianne Gaudric; André J. Smout; Jan Tack; Olivier R. Busch; Giovanni Zaninotto; Guy E. Boeckxstaens

Disclosures

Gastroenterology. 2013;144(4):718-725. 

In This Article

Materials and Methods

Patients

From February 2003 through February 2008 there were 201 patients with achalasia enrolled in the European Achalasia Trial.[12] Patients between 18 and 75 years of age were included at 14 hospitals in 5 European countries and randomized for PD or LHM. The diagnosis of achalasia was based on esophageal manometry showing the absence of peristalsis and impaired LES relaxation (nadir pressure of ≥10 mm Hg during swallow-induced relaxation). In addition, patients had to have an Eckhardt symptom score of more than 3. The Eckardt score (maximum score, 12) is the sum of the symptom scores for dysphagia, regurgitation, and chest pain (0, absent; 1, occasional; 2, daily; and 3, each meal), and weight loss (0, no weight loss; 1, <5 kg; 2, 5–10 kg; and 3, >10 kg). Patients with an esophageal diameter of more than 7 cm were excluded. The study was approved by the Medical Ethics Committee of the Academic Medical Center. Written informed consent was obtained from all subjects before enrolment in the study.

Study Design

Patients were randomized equally for LHM or PD and stratification was performed for hospital and age. The interventions were performed as described previously.[12] In short, for PD a Rigiflex balloon (Boston Scientific, Nanterre, France) was positioned at the esophagogastric junction and dilated with 5 psi for 1 minute, followed by 8 psi for 1 minute. During the first PD a 30-mm balloon was used, followed by dilation with a 35-mm balloon after 1–3 weeks. If 4 weeks later the Eckardt score still was greater than 3, a third dilation with a 40-mm balloon was performed. Patients were considered a failure if the Eckardt score remained greater than 3. Patients with recurrent symptoms during follow-up evaluation were re-dilated with a 35-mm balloon, and, if necessary (Eckardt score still >3), with a 40-mm balloon. A third and final series of dilations was allowed only if symptoms recurred at least 2 years after this second series of dilations.

In patients randomized for LHM, a myotomy was performed extending at least 6 cm over the esophagus above the junction and at least 1–1.5 cm over the stomach. Thereafter, an anterior 180° fundoplication according to Dor[13] was performed to reduce postoperative gastroesophageal reflux. If symptoms recurred after surgery with an Eckardt score greater than 3, the patient was considered to have had treatment failure.

Before treatment, esophageal manometry was performed for the diagnosis of achalasia and to determine LES pressure. Furthermore, a timed barium esophagogram was conducted to quantify esophageal stasis. After treatment, symptom scores were assessed and esophageal manometry and a timed barium esophagogram were performed after 1 month and on a yearly basis. Esophageal manometries were collected retrospectively to determine the type of achalasia. All authors had access to the study data and reviewed and approved the final manuscript.

Manometry

Esophageal manometry was performed using a pneumohydraulic perfusion system and a 6- to 10-channel esophageal manometry catheter with a sleeve sensor incorporated at the distal end. After introduction and equilibration, basal pressure was monitored for at least 5 minutes. LES pressure was determined end-expiratory. The esophageal pressure wave amplitude was analyzed in the 2 channels above the LES. These sensors were located at 3 or 4 cm and at 6 or 8 cm above the LES, depending on the design of the manometric catheter used in the participating centers. Swallow-induced relaxation of the sphincter and esophageal pressure wave amplitude were assessed on 10 consecutive 5-mL wet swallows, at least 30 seconds apart.

Timed Barium Esophagogram

Esophageal stasis was determined on a timed barium esophagogram at 1, 2, and 5 minutes after ingestion of the maximal tolerable amount of low-density barium sulphate over 30–45 seconds without regurgitation or aspiration, with the patient upright in a slight left posterior position.[14] The distance from the tapered distal esophagus to the top of the barium column and the maximal diameter of the esophagus were measured.

Data Analysis

Manometric tracings were reviewed using MMS (Medical Measurements Systems, Enschede, The Netherlands), Medtronic (Medtronic, Minneapolis, MN), or Dynosystem (Memphis, Bologna, Italy) software by 2 reviewers (W.O.R. and R.S.).

We classified the study patients according to their dominant distal esophageal pressurization pattern using modified definitions by Pandolfino et al.[9] Type I achalasia was when 9 of 10 swallows elicited contractions with an amplitude less than 30 mm Hg; type 2 achalasia was when 2 or more contractions had an amplitude greater than 30 mm Hg; and type 3 achalasia was when at least 2 spastic waves were detected (lasting > 6.0 s with an amplitude > 70 mm Hg). These criteria were validated for conventional manometry by Salvador et al.[10]

Parameters of esophageal function (LES pressure, esophageal stasis after 5 minutes, and esophageal width on a timed barium esophagogram) were determined before therapy and at 1 month and yearly after therapy.

Statistical Analysis

Analysis was performed on the modified intention-to-treat population, as previously described.[12] All patients except those in whom a perforation occurred during PD (censored) or those who were lost to follow-up evaluation were included. Protocol violations were considered failures in the modified intention-to-treat analysis. Treatment success was defined as a decrease in Eckardt score to 3 or less, determined at yearly follow-up evaluation. The time to treatment failure was calculated from the day of surgery and the first dilation session until the closing visit or the last visit that was considered part of the follow-up period.

Data were analyzed using SPSS 16.0 (IBM Corporation, Somers, NY). Parametric data are presented as mean ± standard error of the mean, and nonparametric data are presented as median (interquartile range [IQR]). If 3 subtypes were compared, a 1-way analysis of variance (ANOVA) test was used in case of parametric data, and a Kruskal–Wallis test was used in case of nonparametric data. If there was a statistically significant difference a post hoc Student t test or a Mann–Whitney U test was performed with Bonferroni correction. To compare success rates, log-rank tests on Kaplan–Meier estimates were used. A Cox regression model was used to determine risk factors for treatment failure in the 3 subtypes. Repeated measurements of symptom scores and esophageal function after therapy were analyzed with a 2-way repeated-measurements ANOVA. In case of repeated measurement, data are presented as estimated means ± standard error of the mean. All P values were 2-tailed and a P value less than .05 was considered statistically significant.

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